{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:07:48Z","timestamp":1791328068528,"version":"4.3.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD8 T cells need a third signal, along with Ag and costimulation, for effective survival and development of effector functions, and this can be provided by IL-12 or type I IFN. Adoptively transferred OT-I T cells, specific for H-2Kb and OVA, encounter Ag in the draining lymph nodes of mice with the OVA-expressing E.G7 tumor growing at a s.c. site. The OT-I cells respond by undergoing limited clonal expansion and development of effector functions (granzyme B expression and IFN-\u03b3 production), and they migrate to the tumor where they persist but fail to control tumor growth. In contrast, OT-I T cells deficient for both the IL-12 and type I IFN receptors expand only transiently and rapidly disappear. These results suggested that some signal 3 cytokine is available, but that it is insufficient to support a CTL response that can control tumor growth. Consistent with this, administration of IL-12 at day 10 of tumor growth resulted in a large and sustained expansion of wild-type OT-I cells with enhanced effector functions, and tumor growth was controlled. This did not occur when the OT-I cells lacked the IL-12 and type I IFN receptors, demonstrating that the therapeutic effect of IL-12 results from direct delivery of signal 3 to the CD8 T cells responding to tumor Ag in the signal 3-deficient environment of the tumor.<\/jats:p>","DOI":"10.4049\/jimmunol.178.11.6752","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:24:11Z","timestamp":1397863451000},"page":"6752-6760","source":"Crossref","is-referenced-by-count":50,"title":["Signal 3 Availability Limits the CD8 T Cell Response to a Solid Tumor"],"prefix":"10.1093","volume":"178","author":[{"given":"Julie M","family":"Curtsinger","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Y","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra C","family":"Lins","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F","family":"Mescher","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,6,1]]},"reference":[{"key":"2025032803190033100_R1","first-page":"1743","volume-title":"Cancer Res.","year":"2002"},{"key":"2025032803190033100_R2","first-page":"2535","volume-title":"Cancer Res.","year":"2003"},{"key":"2025032803190033100_R3","first-page":"4754","volume-title":"Clin. 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